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1.
PLoS One ; 19(4): e0300307, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635850

RESUMO

This study constructed a multidimensional indicator system to evaluate spatio-temporal heterogeneity of China's import and export trade of 31 provinces from 2000 to 2022. This study describes the distribution of China's import and export trade by using location Gini coefficient and exploratory spatial analysis. Additionally, Multiple linear regression was used to ascertain the extent of contribution by various factors on the spatio-temporal heterogeneity of import and export trade. The simulation results show that inter-provincial import and export trade displayed distinct spatio-temporal differentiation characteristics with a prominent east-to-west disparity from 2000 to 2022. The trade links between various regions of the country have gradually strengthened, with a corresponding high correlation to the level of economic development. GDP, financial expenditure, freight transportation volume, technology market turnover, foreign investment, and disposable income of all residents, significantly influence the per capita export and import volume. In general, it is suggested that China and developing countries should take effective measures to promote balanced trade development, strengthen regional cooperation and coordination, and promote green trade and sustainable development.


Assuntos
Países em Desenvolvimento , Investimentos em Saúde , China , Desenvolvimento Econômico , Análise Espacial
2.
Opt Express ; 32(6): 9433-9441, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571178

RESUMO

Sharp bends are crucial for large-scale and high-density photonics integration on thin-film lithium niobate platform. In this study, we demonstrate low-loss (<0.05 dB) and sharp bends (Reff = 30 µm) using free-form curves with a 200-nm-thick slab and a rib height of 200 nm on x-cut lithium niobate. Employing the same design method, we successfully realize a compact fully-etched ring resonator with a remarkably large free spectral range of 10.36 nm experimentally. Notably, the equivalent radius of the ring resonator is a mere 15 µm, with a loaded Q factor reaching 2.2 × 104.

3.
HLA ; 103(4): e15483, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38605645

RESUMO

HLA-DPB1*1500:01N differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 3.


Assuntos
Cadeias beta de HLA-DP , Nucleotídeos , Humanos , Alelos , Sequência de Bases , China , Análise de Sequência de DNA
4.
Biol Direct ; 19(1): 31, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658981

RESUMO

BACKGROUND: Deubiquitinating enzymes (DUBs) cleave ubiquitin on substrate molecules to maintain protein stability. DUBs reportedly participate in the tumorigenesis and tumour progression of hepatocellular carcinoma (HCC). OTU deubiquitinase 5 (OTUD5), a DUB family member, has been recognized as a critical regulator in bladder cancer, breast cancer and HCC. However, the expression and biological function of OTUD5 in HCC are still controversial. RESULTS: We determined that the expression of OTUD5 was significantly upregulated in HCC tissues. High levels of OTUD5 were also detected in most HCC cell lines. TCGA data analysis demonstrated that high OTUD5 expression indicated poorer overall survival in HCC patients. OTUD5 silencing prominently suppressed HCC cell proliferation, while its overexpression markedly enhanced the proliferation of HCC cells. Mass spectrometry analysis revealed solute carrier family 38 member 1 (SLC38A1) as a candidate downstream target protein of OTUD5. Coimmunoprecipitation analysis confirmed the interaction between OTUD5 and SLC38A1. OTUD5 knockdown reduced and OTUD5 overexpression increased SLC38A1 protein levels in HCC cells. However, OTUD5 alteration had no effect on SLC38A1 mRNA expression. OTUD5 maintained SLC38A1 stability by preventing its ubiquitin-mediated proteasomal degradation. SLC38A1 silencing prominently attenuated the OTUD5-induced increase in HCC cell proliferation. Finally, OTUD5 knockdown markedly suppressed the growth of HCC cells in vivo. CONCLUSIONS: OTUD5 is an oncogene in HCC. OTUD5 contributes to HCC cell proliferation by deubiquitinating and stabilizing SLC38A1. These results may provide a theoretical basis for the development of new anti-HCC drugs.


Assuntos
Carcinoma Hepatocelular , Proliferação de Células , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Ubiquitinação , Endopeptidases/genética , Endopeptidases/metabolismo , Animais , Camundongos , Enzimas Desubiquitinantes/metabolismo , Enzimas Desubiquitinantes/genética , Regulação Neoplásica da Expressão Gênica
5.
Gut Microbes ; 16(1): 2341647, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38659246

RESUMO

The insights into interactions between host genetics and gut microbiome (GM) in colorectal tumor susceptibility (CTS) remains lacking. We used Collaborative Cross mouse population model to identify genetic and microbial determinants of Azoxymethane-induced CTS. We identified 4417 CTS-associated single nucleotide polymorphisms (SNPs) containing 334 genes that were transcriptionally altered in human colorectal cancers (CRCs) and consistently clustered independent human CRC cohorts into two subgroups with different prognosis. We discovered a set of genera in early-life associated with CTS and defined a 16-genus signature that accurately predicted CTS, the majority of which were correlated with human CRCs. We identified 547 SNPs associated with abundances of these genera. Mediation analysis revealed GM as mediators partially exerting the effect of SNP UNC3869242 within Duox2 on CTS. Intestine cell-specific depletion of Duox2 altered GM composition and contribution of Duox2 depletion to CTS was significantly influenced by GM. Our findings provide potential novel targets for personalized CRC prevention and treatment.


Assuntos
Azoximetano , Camundongos de Cruzamento Colaborativo , Neoplasias Colorretais , Microbioma Gastrointestinal , Polimorfismo de Nucleotídeo Único , Animais , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/induzido quimicamente , Humanos , Camundongos , Camundongos de Cruzamento Colaborativo/genética , Oxidases Duais/genética , Oxidases Duais/metabolismo , Predisposição Genética para Doença , Masculino , Bactérias/genética , Bactérias/classificação , Bactérias/metabolismo , Bactérias/isolamento & purificação , Modelos Animais de Doenças , Feminino
6.
Chemistry ; : e202304315, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581408

RESUMO

Developing efficient catalysts to convert CO2 into value-added chemicals is valuable for reducing carbon emissions. Herein, a kind of novel thiolate-based ionic liquid with sulfur as the active site was designed and synthesized, which served as highly efficient catalyst for the reductive N-functionalization of CO2 by amines and hydrosilane. By adjusting the CO2 pressure, various N-formamides and N-methylamines were selectively obtained in high yields. Remarkably, at the catalyst loading of 0.1 mol %, the N-formylation reaction of N-methylaniline exhibited an impressive turnover frequency (TOF) up to 600 h-1, which could be attributed to the roles of the ionic liquids in activating hydrosilane and amine. In addition, control experiments and NMR monitoring experiments provided evidence that the reduction of CO2 by hydrosilane yielded formoxysilane intermediates that subsequently reacted with amines to form N-formylated products. Alternatively, the formoxysilane intermediates could further react with hydrosilane and amine to produce 4-electron-reduced aminal products. These aminal products served as crucial intermediates in the N-methylation reactions.

7.
Cancer Med ; 13(7): e7136, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38545767

RESUMO

BACKGROUND: The death burden attributable to modifiable risk factors is key to colorectal cancer (CRC) prevention. This study aimed to assess the prevalence and regional distribution of attributable CRC death burden worldwide from 1990 to 2019. METHODS: We extracted data from the Global Burden of Disease Study in 2019 and assessed the mortality, age-standardized death rate (ASDR), population attributable fractions, and time trend in CRC attributable to risk factors by geography, socio-demographic index (SDI) quintile, age, and sex. RESULTS: Over the past 30 years, from high to low SDI region, the number of deaths increased by 46.56%, 103.55%, 249.64%, 231.89%, 163.11%, and the average annual percentage change (AAPC) for ASDR were -1.06%, -0.01%, 1.32%, 1.19%, and 0.65%, respectively. ASDR in males was 1.88 times than in females in 2019; ASDR in males showed an increasing trend (AAPC 0.07%), whereas ASDR in females showed a decreasing trend (AAPC -0.69%) compared to figures in 1990. In 2019, from high to low SDI region, the 15-49 age group accounted for 3%, 6%, 10%, 11%, and 15% of the total population; dietary and metabolic factors contributed 43.4% and 20.8% to CRC-attributable death worldwide. From high to low SDI region, ASDRs caused by dietary and metabolic factors increased by -23.4%, -5.5%, 25.8%, 29.1%, 13.5%, and 1.4%, 33.3%, 100.8%, 128.4%, 77.7% respectively, compared to 1990. CONCLUSIONS: The attributable CRC death burden gradually shifted from higher SDI to lower SDI regions. The limitation in males was more significant, and the gap is expected to be further expanded. In lower SDI regions, the death burden tended to affect younger people. The leading cause of CRC-attributable deaths was the inadequate control of dietary and metabolic risk factors.


Assuntos
Neoplasias Colorretais , Feminino , Masculino , Humanos , Fatores de Risco , Geografia , Neoplasias Colorretais/epidemiologia , Saúde Global
8.
Microbiol Spectr ; 12(4): e0115423, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38441468

RESUMO

Previous studies have profiled the gut microbiota among psoriatic patients compared to that among healthy individuals. However, a comprehensive understanding of the magnitude, direction, and detailed compositional and functional profiles remains limited. Additionally, research exploring the gut microbiota in the context of both plaque psoriasis (PsO) and psoriatic arthritis (PsA) is lacking. To assess the taxonomic and functional characteristics of the gut microbiota in PsO and PsA patients and investigate potential links between the gut microbiota and disease pathogenesis. We collected fecal samples from 70 psoriatic patients (44 PsO and 26 PsA) and 25 age- and gender-matched healthy controls (HC) and employed deep metagenomic sequencing to characterize their gut microbiota. We noted significant alternations in the gut microbiota compositions of both PsO and PsA patients compared to those of HC. Despite limited effect sizes in alpha diversity (12.3% reduction of microbial richness but unchanged evenness in psoriatic patients) and beta diversity (disease accounts for 3.5% of total variations), we consistently observed substantial reductions of Eubacterium rectale in both PsO and PsA patients, with PsA patients exhibiting even lower levels of E. rectale than PsO patients. Additionally, two Alistipes species were also depleted in psoriatic patients. These microorganisms are known to play crucial roles in carbohydrate metabolism pathways, mainly producing short-chain fatty acids with anti-inflammatory effects. Overall, our observations supplemented the profiling of altered gut microbiota in patients with PsO and PsA at the species level and described a link between the dominant short-chain fatty acid-producing bacterial species and systemic immunity in psoriatic patients. IMPORTANCE: In this observational clinical study with sufficient sample size and metagenomic sequencing to profile the gut microbiota, we identified consistent signals of the depleted abundance of Eubacterium rectale and related functional genes among psoriatic patients, including those with psoriatic arthritis. E. rectale may serve as an ecologically important functional unit in the gut microbiota, holding potential as a diagnostic marker and target for therapeutic interventions to achieve lasting effects. Our findings provide comprehensive gut microbiota profiling in psoriasis, resolving previous contradictions and generating new hypotheses for further investigation. These insights may significantly impact psoriasis management and related conditions.


Assuntos
Artrite Psoriásica , Microbioma Gastrointestinal , Psoríase , Humanos , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/metabolismo , Eubacterium , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/metabolismo , Fezes
9.
Front Microbiol ; 15: 1298106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38380105

RESUMO

Porcine circovirus type 2 (PCV2) is the etiological agent of PCV2-associated diseases that pose a serious threat to the swine industry. PCV2 capsid (Cap) protein has been shown to interact with DEAD-box RNA helicase 21 (DDX21), an important protein that regulates RNA virus replication. However, whether the interaction between DDX21 and the PCV2 Cap regulates PCV2 replication remains unclear. Herein, by using western blotting, interaction assays, and knockdown analysis, we found that PCV2 infection induced the cytoplasmic relocation of DDX21 from the nucleolus in cultured PK-15 cells. Moreover, the nuclear localization signal (NLS) of PCV2 Cap interacted directly with DDX21. The NLS of PCV2 Cap and 763GSRSNRFQNK772 residues at the C-terminal domain (CTD) of DDX21 were essential for the dual interaction. Upon shRNA-mediated DDX21 depletion in PK-15 cells, we observed impaired PCV2 replication via a lentivirus-delivered system, as evidenced by decreased levels of viral protein expression and virus production. In contrast, the replication of PCV2 increased in transiently DDX21-overexpressing cells. Our results indicate that DDX21 interacts with PCV2 Cap and plays a crucial role in virus replication. These results provide a reference for developing novel potential targets for prevention and control of PCV2 infection.

10.
BMC Public Health ; 24(1): 353, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308244

RESUMO

BACKGROUND: Smoke exposure is a prevalent and well-documented risk factor for various diseases across different organ systems. Serum neurofilament light chain (sNfL) has emerged as a promising biomarker for a multitude of nervous system disorders. However, there is a notable paucity of research exploring the associations between smoke exposure and sNfL levels. METHODS: We conducted a comprehensive analysis of the National Health and Nutrition Examination Survey (NHANES) cross-sectional data spanning the years 2013 to 2014. Serum cotinine levels were classified into the following three groups: < 0.05, 0.05-2.99, and ≥ 3 ng/ml. Multiple linear regression models were employed to assess the relationships between serum cotinine levels and sNfL levels. Additionally, we utilized restricted cubic spline analyses to elucidate the potential nonlinear relationship between serum cotinine and sNfL levels. RESULTS: A total of 2053 participants were included in our present research. Among these individuals, the mean age was 47.04 ± 15.32 years, and males accounted for 48.2% of the total study population. After adjusting the full model, serum cotinine was positively correlated with sNfl in the second group (ß = 0.08, 95%CI 0.01-0.15) and in the highest concentration of serum cotinine (ß = 0.10, 95%CI 0.01-0.19) compared to the group with the lowest serum cotinine concentrations. Current smokers, in comparison to non-smokers, exhibited a trend toward elevated sNfL levels (ß = 0.07, 95%CI 0.01-0.13). Furthermore, subgroup analyses revealed interactions between serum cotinine levels and different age groups (P for interaction = 0.001) and gender stratification (P for interaction = 0.015) on sNfL levels. CONCLUSION: The study suggested that serum cotinine was significantly and positively associated with sNfl levels in adult participants. Furthermore, current smokers tend to exhibit elevated sNfL levels. This research sheds light on the potential implications of smoke exposure on neurological function impairment and underscores the importance of further exploration in this area.


Assuntos
Poluição por Fumaça de Tabaco , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Estudos Transversais , Inquéritos Nutricionais , Cotinina/análise , Filamentos Intermediários/química , Biomarcadores
11.
Int J Nanomedicine ; 19: 1431-1450, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38371455

RESUMO

Introduction: Basic fibroblast growth factor (bFGF) shows great potential for preventing vascular dementia (VD). However, the blood‒brain barrier (BBB) and low bioavailability of bFGF in vivo limit its application. The present study investigated how nasal administration of bFGF-loaded nanoliposomes (bFGF-lips) affects the impaired learning and cognitive function of VD mice and the underlying mechanism involved. Methods: A mouse model of VD was established through repeated cerebral ischemia‒reperfusion. A Morris water maze (MWM) and novel object recognition (NOR) tests were performed to assess the learning and cognitive function of the mice. Hematoxylin and eosin (HE) staining, Nissl staining and TUNEL staining were used to evaluate histopathological changes in mice in each group. ELISA and Western blot analysis were used to investigate the molecular mechanism by which bFGF-lips improve VD incidence. Results: Behavioral and histopathological analyses showed that cognitive function was significantly improved in the bFGF-lips group compared to the VD and bFGF groups; in addition, abnormalities and the apoptosis indices of hippocampal neurons were significantly decreased. ELISA and Western blot analysis revealed that bFGF-lips nasal administration significantly increased the concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), bFGF, B-cell lymphoma 2 (Bcl-2), phosphorylated protein kinase B (PAKT), nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO1) and haem oxygenase-1 (HO-1) in the hippocampus of bFGF-lips mice compared with the VD and bFGF groups. Furthermore, the concentrations of malondialdehyde (MDA), caspase-3 and B-cell lymphoma 2-associated X (Bax) were clearly lower in the bFGF-lips group than in the VD and bFGF groups. Conclusion: This study confirmed that the nasal administration of bFGF-lips significantly increased bFGF concentrations in the hippocampi of VD mice. bFGF-lips treatment reduced repeated I/R-induced neuronal apoptosis by regulating apoptosis-related protein concentrations and activating the phosphatidylinositol-3-kinase (PI3K)/(AKT)/Nrf2 signaling pathway to inhibit oxidative stress.


Assuntos
Isquemia Encefálica , Demência Vascular , Camundongos , Animais , Demência Vascular/tratamento farmacológico , Demência Vascular/metabolismo , Demência Vascular/patologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Administração Intranasal , Estresse Oxidativo , Infarto Cerebral , Isquemia Encefálica/tratamento farmacológico , Cognição , Reperfusão , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Apoptose
12.
Artigo em Inglês | MEDLINE | ID: mdl-38376700

RESUMO

Coronary atherosclerosis leading to ischemic artery disease is one of the etiological factors to develop heart failure (HF). This study aimed to investigate potential biomarkers for discriminating HF in atherosclerotic patients. This study included 40 consecutive atherosclerotic patients who underwent angiography. Concentrations of B-type natriuretic peptide (BNP), fibronectin type III domain containing 5 (FNDC5), and Phosphodiesterase 9A (PDE9A) were measured in 20 atherosclerotic patients with HF symptoms/signs and 20 without HF symptoms/signs. Circulating BNP levels were elevated, while FNDC5 levels were reduced in atherosclerotic patients with HF symptoms/signs compared to those without HF symptoms/signs. Pearson correlation analysis showed a significant correlation between FNDC5 and BNP. Receiver Operating Characteristics analysis indicated that both FNDC5 and BNP were able to discriminate HF in atherosclerotic patients. Our findings suggest that FNDC5, along with BNP, has independent value as a biomarker for discriminating HF in patients with coronary atherosclerosis.

13.
Bioresour Technol ; 395: 130335, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38242237

RESUMO

This study presented the effects of hydrochar on humification, heavy metals (HMs) bioavailability and bacterial community succession during composting. Results indicated that hydrochar addition led to elevated composting temperature, 7.3% increase in humic acid (HA), and 52.9% increase in ratio of humic acid to fulvic acid. The diethylene triamine pentacetic acid extractable Zn, Cu, Pb, and Ni were reduced by 19.2%, 36.3%, 37.8%, and 27.1%, respectively, in hydrochar-involved composting system. Furthermore, main mechanisms driving the reduced HMs bioavailability by hydrochar addition were revealed. The addition of hydrochar significantly modified the microbial community structure. Correlation analysis and microbial analysis demonstrated that relative abundance of bacterial groups connected with humification and HMs passivation were increased. Consequently, the HA formation was promoted and the HMs bioavailability were reduced through bacterial bioremediation and HA complexation. This study demonstrates the addition of hydrochar as a promising strategy to mitigate the HMs bioavailability during composting.


Assuntos
Compostagem , Metais Pesados , Microbiota , Substâncias Húmicas , Solo/química , Disponibilidade Biológica , Esterco , Metais Pesados/análise
14.
Cell Mol Neurobiol ; 44(1): 16, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38198062

RESUMO

Circular RNA circSKA3 (spindle and kinetochore-related complex subunit 3) has been identified as a prognostic factor in ischemic stroke. The objective of this study was to investigate the association of circSKA3 with the risk of extracranial artery stenosis (ECAS) and plaque instability in patients with ischemic stroke. We constructed a competing endogenous RNA (ceRNA) network regulated by circSKA3 based on differentially expressed circRNAs and mRNAs between five patients and five controls. Gene Ontology (GO) analysis was performed on the 65 mRNAs within the network, revealing their primary involvement in inflammatory biological processes. A total of 284 ischemic stroke patients who underwent various imaging examinations were included for further analyses. Each 1 standard deviation increase in the log-transformed blood circSKA3 level was associated with a 56.3% increased risk of ECAS (P = 0.005) and a 142.1% increased risk of plaque instability (P = 0.005). Patients in the top tertile of circSKA3 had a 2.418-fold (P < 0.05) risk of ECAS compared to the reference group (P for trend = 0.02). CircSKA3 demonstrated a significant but limited ability to discriminate the presence of ECAS (AUC = 0.594, P = 0.015) and unstable carotid plaques (AUC = 0.647, P = 0.034). CircSKA3 improved the reclassification power for ECAS (NRI: 9.86%, P = 0.012; IDI: 2.97%, P = 0.007) and plaque instability (NRI: 36.73%, P = 0.008; IDI: 7.05%, P = 0.04) beyond conventional risk factors. CircSKA3 played an important role in the pathogenesis of ischemic stroke by influencing inflammatory biological processes. Increased circSKA3 was positively associated with the risk of ECAS and plaque instability among ischemic stroke patients.


Assuntos
AVC Isquêmico , Humanos , Constrição Patológica , AVC Isquêmico/complicações , AVC Isquêmico/genética , Fatores de Risco , Ontologia Genética , RNA Circular , RNA Mensageiro , Artérias
15.
Cell Rep Med ; 5(1): 101355, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38194971

RESUMO

Despite the encouraging efficacy of anti-PD-1/PD-L1 immunotherapy in microsatellite-instability-high/deficient mismatch repair (MSI-H/dMMR) advanced gastrointestinal cancer, many patients exhibit primary or acquired resistance. Using multi-omics approaches, we interrogate gut microbiome, blood metabolome, and cytokines/chemokines of patients with MSI-H/dMMR gastrointestinal cancer (N = 77) at baseline and during the treatment. We identify a number of microbes (e.g., Porphyromonadaceae) and metabolites (e.g., arginine) highly associated with primary resistance to immunotherapy. An independent validation cohort (N = 39) and mouse model are used to further confirm our findings. A predictive machine learning model for primary resistance is also built and achieves an accuracy of 0.79 on the external validation set. Furthermore, several microbes are pinpointed that gradually changed during the process of acquired resistance. In summary, our study demonstrates the essential role of gut microbiome in drug resistance, and this can be utilized as a preventative diagnosis tool and therapeutic target in the future.


Assuntos
Neoplasias Encefálicas , Neoplasias Colorretais , Microbioma Gastrointestinal , Neoplasias Gastrointestinais , Síndromes Neoplásicas Hereditárias , Animais , Camundongos , Humanos , Ecossistema , Microbioma Gastrointestinal/genética , Multiômica , Mutação , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/terapia , Imunoterapia , Repetições de Microssatélites
16.
Appl Biochem Biotechnol ; 196(1): 182-202, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37103738

RESUMO

The non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. It is usually diagnosed at an advanced stage with poor prognosis. Nimbolide (NB), a terpenoid limonoid isolated from the flowers and leaves of neem tree, possesses anticancer properties in various cancer cell lines. However, the underlying mechanism of its anticancer effect on human NSCLC cells remains unclear. In the present study, we investigated the effect of NB on A549 human NSCLC cells. We found that NB treatment inhibits A549 cells colony formation in a dose-dependent manner. Mechanistically, NB treatment increases cellular reactive oxygen species (ROS) level, leading to endoplasmic reticulum (ER) stress, DNA damage, and eventually induction of apoptosis in NSCLC cells. Furthermore, all these effects of NB were blocked by pretreatment with antioxidant glutathione (GSH), the specific ROS inhibitor. We further knockdown CHOP protein by siRNA markedly reduced NB-induced apoptosis in A549 cells. Taken together, our findings reveal that NB is an inducer of ER stress and ROS; these findings may contribute to increasing the therapeutic efficiency of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Limoninas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Limoninas/farmacologia , Limoninas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Dano ao DNA , Estresse do Retículo Endoplasmático/genética , Linhagem Celular Tumoral
17.
Mater Horiz ; 11(4): 995-1007, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38047955

RESUMO

Transcutaneous energy-harvesting technology based on ultrasound-driven piezoelectric nanogenerators is the most promising technology in medical and industrial applications. Based on ultrasonic coupling effects at the interfaces, the interfacial architecture is a critical parameter to attain desirable electromechanical properties of nanocomposites. Herein, we successfully synthesized core-conductive shell-structured BaTiO3@Carbon [BT@Carbon] nanoparticles [NPs] as nanofillers to design implantable poly(vinylidenefluoride-co-chlorotrifluoroethylene)/BT@Carbon [P(VDF-CTFE)/BT@Carbon] piezoelectric nanogenerators (PENGs) and actuators for harvesting ultrasound (US) underneath the skin. For US-driven PENGs, the electrons and holes are generated not only from the interfaces between the BT@Carbon NPs and the matrix, but also from the dipoles vibrating in the smaller lamellae of ferroelectric ß-phase crystals in poled nanocomposites. Remarkably, P(VDF-CTFE)/BT@Carbon piezoelectric nanogenerators could attain an extraordinary output power of 521 µW cm-2 under ultrasound stimulation, which is far greater than that of force-induced PVDF-based nanogenerators and other ultrasound-driven triboelectric generators. Furthermore, the US-PENG actuator system, which is composed of an amplifier and a microcontroller, could efficiently convert ultrasonic energy into electricity or instructions to switch on/off small electronics in the tissues and organs of mice. Finally, the nanocomposite-based US-driven PENGs have a good biocompatibility, with no cytotoxicity or immune response in vivo, indicating their potential for developing wireless power generators and actuators for medical implant devices.

18.
Heliyon ; 9(11): e22092, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38058653

RESUMO

Colorectal cancer (CRC) is one of the most common malignancies, and at the initial visit, most patients are diagnosed with metastatic CRC (mCRC). However, immunotherapy is only and highly effective in a very small proportion of patients with mCRC having mismatch repair defect (dMMR)/high microsatellite instability, and the majority of the patients with mCRC having mismatch repair proficient (pMMR)/microsatellite stability (MSS) cannot benefit from it. At present, many clinical studies of immunotherapy combined with tyrosine kinase inhibitors (TKIs) are trying to regulate the immune microenvironment of pMMR/MSS mCRC, transforming a "cold tumor" into a "hot tumor," which has not only surprising effects but also certain limitations, i.e., the response could not be specific to metastasis. Therefore, regarding the bottleneck encountered by immunotherapy in patients with patients pMMR/MSS mCRC, this study summarized current research and possible mechanisms of immunotherapy combined with local therapy for metastasis, including radiotherapy, ablation, and transcatheter arterial chemoembolization.

19.
Med Teach ; : 1-5, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38146748

RESUMO

The current medical model has transitioned from the original biomedical treatment model to a bio-psycho-social model, where patients now have higher demands for service awareness. Consequently, doctor-patient relationships have become a crucial aspect of the contemporary medical process. Currently, psychological resilience among medical students in China tends to be at a moderately lower level. Medical students often exhibit poor psychological qualities in handling contradictions in doctor-patient relationships. Moreover, there is a lack of emphasis on the education of corresponding psychological qualities for medical students during the teaching process. This deficiency is highly disadvantageous for medical students in their future management of doctor-patient relationships. The article explores how to cultivate psychological resilience in medical students and enhance their ability to handle conflicts in doctor-patient relationships from the perspective of doctor-patient relationships. The author suggests that schools should place greater emphasis on the psychological resilience of medical students, change teaching methods, incorporate online education to enhance the mentalization level of medical students, and propose an eight-week mindfulness cognitive therapy program to improve psychological resilience. The intervention process should consider establishing positive coping mechanisms, promoting good interpersonal relationships among medical students, and regulating individual negative emotions. Through simulating doctor-patient scenarios, teachers should consciously train the psychological resilience of medical students, improve their cognition and thinking abilities, and accelerate their psychological health recovery.

20.
Medicine (Baltimore) ; 102(50): e36370, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38115358

RESUMO

INTRODUCTION: A systematic review and meta-analysis were conducted to evaluate the efficacy and the overall safety of Faricimab compared with other anti-vascular endothelial growth factors (VEGF) therapy for neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME). MATERIALS AND METHODS: A systematic literature search of a comprehensive electronic database was performed to identify randomized clinical trials published from January 2013 to January 2023 for Faricimab in AMD and DME. Weighted mean differences and risk ratios were used to integrate the different studies. RESULTS: A total of 4 randomized controlled trials (RCTs) with 1678 AMD patients and 3 RCTs with 20 DME patients were included in the meta-analysis.In patients with AMD, a significant difference was found in the number of injections between Faricimab and other anti-VEGF therapy (MD = -2.42, 95% CI [-3.93 to -0.90], P = .002).No significant difference was found for the change in best corrected visual acuity (BVCA), central subfoveal thickness (CST), and gaining 15 or more letters. Similarly, no significant difference was found for adverse events.In patients with DME, a significant difference was observed for CST (MD = -22.41, 95% CI [-29.95 to -14.86], P < .00001) and the number of injections(MD = -0.93, 95% CI [-1.33 to -0.54], P < .00001). No significant difference was found for BVCA and gaining 15 or more letters, and no significant difference was found for adverse events. CONCLUSIONS: Comprehensive evidence confirms that Faricimab achieves non-inferior or even better CST improvement than other anti-VEGF therapies with extended dosing intervals, but more long-term follow-up studies are needed to support our conclusions.


Assuntos
Anticorpos Biespecíficos , Complicações do Diabetes , Degeneração Macular , Edema Macular , Fator A de Crescimento do Endotélio Vascular , Anticorpos Biespecíficos/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular/terapia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Edema Macular/etiologia , Edema Macular/terapia , Complicações do Diabetes/terapia , Resultado do Tratamento
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